The objective of this research proposal is to examine the chemical correlates in the brain of various behavioral changes mediated or induced by neuroendocrinological alterations. These chemical studies will examine the metabolic events occurring in the hypothalamus associated with behavioral and endocrinological changes. Detailed chemical analyses will be made of specific hypothalamic nuclei which are thought to control sexual behavior and reproductive physiology and of the extrahypothalamic structures such as the limbic system which modulate these phenomena. These hypothalamic nuclei are those in the anterior, middle, and posterior hypothalamus which have been shown, by electrical stimulation, lesions, stereotaxic hormone implantation, autoradiographic studies of hormone uptake, and neonatal hormone administration, to play an important role in neuroendocrine control. The metabolic parameters will be measured during sexual development and behavior, the estrous cycle, after gonadectomy, after androgen sterilization, and following morphine administration. The techniques of quantitative histochemistry and immunochemistry will be used. Quantitative chemical measurements will be performed on samples weighing 10 to 20 ng, obtained by dissection of discrete, histologically defined nuclear areas of the hypothalamus in freeze-dried, unfixed, unstained tissue sections. To determine the precise specificity of these metabolic events, nuclei from other areas of the hypothalamus not involved in control of these functions and other areas of the brain, e.g., cerebral cortex and cerebellum, will also be analyzed. Analyses will be performed for enzymes reflecting the over-all metabolic flow through a pathway, control point enzymes, enzymes in pathway unique to brain, lysosomal enzymes, biogenic amines and enzymes associated with their metabolism, brain specific proteins and neuronal nucleic acids. In addition, measurement of pituitary gonadotropins and target organ hormones, testosterone and estrogen, will be made to provide an important supplement to the metabolic data.